BIOSPECIMEN CORE - CORE D: ABSTRACT Biomarkers for Older Controls At Risk for Dementia (BIOCARD) STUDY The Biospecimen Core (Core D) is responsible for all aspects of cerebrospinal fluid (CSF) and blood collection, storage, and analysis. The aims of the Biospecimen Core are: The specific aims of Biospecimen Core are: (1) Collect, catalog, and store CSF and blood specimens from participants in the BIOCARD study and from patients in the Johns Hopkins CSF Disorders Center (the latter to be used for exploratory analyses). CSF collection will be reinitiated biannually in the BIOCARD cohort, to add to the existing specimens. (2) Perform AlzBio3 assays for CSF A?1-42, total tau, and ptau-181 and an MSD assay for A?1-42 on all newly collected CSF specimens from BIOCARD participants and from well characterized patients in the Johns Hopkins CSF Disorders Center, and compare the validity of the two assays for A?1-42. (3) Examine the utility of new CSF assays as Alzheimer's disease (AD) biomarkers, using samples from patients in the Johns Hopkins CSF Disorders Center for discovery, and from participants in the BIOCARD cohort for validation. These assays will include: (a) a multiplexed assay for inflammatory markers, (b) a proteomics assay for synaptic markers and (c) a metabolomic assay for small molecules.